Fesoterodine treatment of pediatric patients with neurogenic detrusor overactivity: A 24-week, randomized, open-label, phase 3 study

• Published in: Journal of pediatric urology 2023-04, Vol.19 (2), p.175.e1-175.e10
• Main Authors: Kitta, Takeya, Darekar, Amanda, Malhotra, Bimal, Shahin, Mohamed H., Jones, Philip, Lindsay, Monica, Mallen, Sharon, Nieto, Alejandra, Crook, Tim J.
• Format: Article
• Language: English
• Subjects: Adolescent; Anticholinergic; Antimuscarinics; Child; Clinical study; Humans; Mandelic Acids - pharmacology; Mandelic Acids - therapeutic use; Muscarinic Antagonists - therapeutic use; Neurogenic detrusor overactivity; Pediatrics; Therapeutics; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive - complications; Urinary Incontinence - drug therapy; Urodynamics - physiology
• ISSN: 1477-5131; 1873-4898
• DOI: 10.1016/j.jpurol.2022.11.020

Neurogenic detrusor overactivity (NDO) can damage the upper urinary tract leading to chronic renal impairment. Antimuscarinic therapy is used to improve urinary incontinence and protect the upper urinary tract in patients with NDO. This study investigated safety and efficacy of fesoterodine, a muscarinic receptor antagonist, in 6‒25 kg) were randomized to fesoterodine 4 or 8 mg extended-release tablets or oxybutynin XL tablets administered over the 12-week active comparator-controlled phase. The safety extension phase evaluated fesoterodine 4 and 8 mg for a further 12 weeks, with patients in the oxybutynin arm allocated to fesoterodine 4 or 8 mg. Patients in Cohort 2 (bodyweight ≤25 kg) were randomized to fesoterodine 2 or 4 mg extended-release beads-in-capsule (BIC) administered over a 12-week efficacy phase and 12-week safety extension phase. Patients with stable neurologic disease and clinically or urodynamically proven NDO were included. The primary endpoint was change from baseline to Week 12 in maximum cystometric bladder capacity (MCC). Secondary efficacy endpoints included detrusor pressure at maximum bladder capacity, bladder volume at first involuntary detrusor contraction, bladder compliance, and incontinence episodes. Safety endpoints included adverse event incidence, and specific assessments of cognition, behavior and vision. The pharmacokinetics of 5-hydroxymethyl tolterodine (5-HMT; fesoterodine’s active metabolite) was determined using population-pharmacokinetic analysis. In Cohort 1 (n = 124), fesoterodine 4 and 8 mg treatment resulted in significant increases from baseline in the primary endpoint of MCC at Week 12. In Cohort 2 (n = 57), fesoterodine 2 and 4 mg BIC treatment resulted in improvements in MCC from baseline. Fesoterodine 4 and 8 mg and fesoterodine 4 mg BIC led to improvements in some secondary efficacy endpoints. The most common treatment-related adverse reactions were gastrointestinal effects, such as dry mouth, which occurred more frequently with oxybutynin than fesoterodine. No detrimental effects on visual accommodation or acuity, or on cognitive function or behavior were observed. These safety and efficacy results are consistent with limited published data on fesoterodine treatment in pediatric populations with overactive bladder or NDO. Study limitations include the lack of placebo